Hydroxychloroquine and risk of cardiac decompensation

Case Report | DOI: https://doi.org/10.31579/2690-4861/053

Hydroxychloroquine and risk of cardiac decompensation

  • Lindsey Tilling 1*

1 Royal Berkshire Hospital Reading; Dr Sacha Bull, Royal Berkshire Hospital Reading RG1 5AN UK.

*Corresponding Author: Dr Lindsey Tilling, Royal Berkshire Hospital, Craven Road, Reading RG1 5AN UK. Telephone 0118 322 7312.

Citation: Tilling L. (2020) Hydroxychloroquine and risk of cardiac decompensation. International Journal of Clinical Case Reports and Reviews. 4(2); DOI: 10.31579/2690-4861/053

Copyright: © 2020 Lindsey Tilling, This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 06 September 2020 | Accepted: 03 November 2020 | Published: 06 November 2020

Keywords: hydroxychloroquine; covid-19; systolic impairment

Abstract

Background
Hydroxychloroquine (HCQ) is a 4-aminoquinoline derivative, used in the treatment of malaria and rheumatic diseases. HCQ has also been suggested as a treatment in patients suffering from severe acute respiratory syndrome–coronavirus 2 (SARS–CoV-2). One of the cardiac complications of SARS-CoV-2 is myocarditis and ventricular dysfunction.
Case summary
We present the case of a 52 year old lady presenting with 2 months history of breathlessness, found to have severely impaired left ventricular function. She had been taking HCQ for 28 months for seronegative inflammatory arthritis. No cause was identified on initial investigation.  She was treated with optimal medical therapy, and HCQ was stopped. After 5 months a cardiac MRI scan revealed full remodelling of the ventricle.
Discussion
This case highlights one of the lesser recognized side effects of HCQ, and the potential for severe cardiac dysfunction. As this drug continues to be investigated and used in the management of SARS-CoV-2 it is important to recognize the potential for cardiac decompensation in patients who are already at increased risk of myocardial dysfunction.

Introduction

Hydroxychloroquine (HCQ) is a 4-aminoquinoline derivative, used in the treatment of malaria and rheumatic diseases. HCQ has also been suggested as a treatment in patients suffering from severe acute respiratory syndrome–coronavirus 2 (SARS–CoV-2). Activity against coronavirus and influenza has been demonstrated in vitro, and in small clinical studies, the majority uncontrolled. SARS-CoV-2 typically presents with cough, fever and fatigue, although other presentations are recognised, including heart failure and myocarditis.

There is understandable urgency in finding a treatment for this disease which has significant mortality, but concern persists regarding the efficacy of HCQ in the management of SARS-CoV-2, and also the potential for harm. Side effects of HCQ are rare, but may include adverse effects on the eye, gastrointestinal tract, and skin. Arrhythmia, and prolongation of the QT interval are recognized as the main cardiac adverse events, with cardiomyopathy infrequently recorded.

Timeline

table

Case presentation

A 52 year old female teaching assistant presented to the emergency department with 2 months of exertional breathlessness. Her exercise tolerance had significantly diminished from normal to only 10 yards. She also reported non-exertional chest and abdominal pains. She had a background of controlled hypertension, fibromyalgia, and seronegative inflammatory arthritis, for which she had been taking methotrexate for 2 years, and HCQ 200mg twice daily for 28 months. Grade 2, ER positive, HER2 negative invasive ductal carcinoma had been diagnosed 18 months earlier, and treated with wide local excision and radiotherapy. Other medications included indapamide, amlodipine, anastrozole and gabapentin.

There was no family history of ischaemic heart disease, cardiomyopathy or sudden death in her family. She was previously fully independent, was a non-smoker, and reported infrequent alcohol consumption.

On examination weight was 95kg and BMI 35, temperature 36.9. Pulse 108 beats per minute, blood pressure 132/91mmHg, oxygen saturations 98% on air. Right base crepitations were audible, with otherwise unremarkable cardiovascular and abdominal examination.

Blood tests revealed a normocytic mild anaemia, normal renal function, and deranged liver function which became progressively worse during admisson, but had resolved by the first clinic appointment post discharge. At peak ALP was 175IU, ALT 1643IU. D Dimer was also elevated at 2696mg/ml, troponin T slightly high at 26ng/L and NTproBNP 1450pg/ml (table 1). Autoimmune screen was negative as were hepatitis and HIV screen, and iron studies and thyroid function were normal.

Table i. Laboratory values during inpatient stay (day 1-9) and at first clinic visit (day 26)

Abbreviations: eGFR estimated glomerular filtration rate; ALP alkaline phosphatase; ALT alanine aminotransferase; NTproBNP N-terminal pro-hormone B natriuretic peptide

Her ECG showed a sinus tachycardia, with T wave inversion in V1-4 (Figure 1)

Figure

Chest xray was unremarkable. CT pulmonary angiogram showed no pulmonary emboli, a small right sided pleural effusion, and otherwise clear lung fields. Ultrasound of the abdomen showed a mildly fatty abdomen only.

Transthoracic echo demonstrated a severely impaired left ventricle, with septal dyskinesis, overall ejection fraction estimated at 15%. The right heart was also impaired, and there was evidence of moderate functional mitral regurgitation and tricuspid regurgitation (Video 1, 2 and 3).

Management

The patient was treated with intravenous diuretics and commenced on ramipril 2.5mg once daily and bisoprolol 5mg twice daily. Methotrexate was stopped in view of the liver dysfunction, and her liver dysfunction improved during the admission. At clinic review 3 weeks post discharge she remained very breathless. Ramipril was increased to 3.75mg once daily, ivabradine 5mg twice daily initiated, and she was advised to discontinue HCQ in view of the potential for drug-induced cardiomyopathy. 5 months later she underwent a cardiac MRI scan. This demonstrated a fully remodelled left and right ventricle, with no late gadolinium enhancement of the left ventricle. (Video 3 and 4).

Our patient reported some improvement in her symptoms of breathlessness when reviewed 5 months after initial diagnosis, and there has been no progression in her rheumatological symptoms. She remains on heart failure medication.

Discussion

This patient presented in decompensated, newly diagnosed heart failure with severely reduced ejection fraction. Withdrawal of a medication which is known to cause cardiac failure led to full remodelling of the ventricles, and this, in the absence of any other cause of heart failure leads us to believe HCQ to be causative.

HCQ-induced cardiomyopathy has been associated with female gender, older age, prolonged duration of therapy and pre-existing cardiovascular disease. Pre-existing cardiac disease has also been recognised as a risk factor for worse outcomes for patients with SARS-CoV-2 [1, 2]. 

Initial echocardiogram findings in HCQ-induced cardiomyopathy may include hypertrophy, biatrial enlargement and restrictive physiology, preceding systolic impairment, which is often severe [3]. In cases where the diagnosis is unclear, cardiac biopsy has been carried out; the characteristic findings are of diffuse myocyte vacuolization without myocarditis on histology, and sarcoplasmic myelinoid and curvilinear bodies on electron microscopy [4]. One recent case report noted that, within 6 months of drug withdrawal, cardiomyocytes were reduced in size and devoid of intracellular vacuoles and myelin and curvilinear bodies were replaced by new contractile elements [5].

Cardiomyopathy associated with HCQ use can be fatal.  In a review of 25 patients taking HCQ or chloroquine and new onset heart failure 12 ceased therapy, 8 of these improved clinically, and 4 required cardiac transplantation, or died [6]. It is suggested that failure to recognise HCQ induced cardiomyopathy may contribute to poorer outcomes, as a result of delayed diagnosis.

The FDA has very recently authorized HCQ for use in patients hospitalized with SARS-CoV-2. This was following small studies which indicated reduced time to clinical recovery, and in this setting, HCQ was only given for short periods, typically <7 days [7]. It is worth noting that these patients may however have pre-existing cardiovascular disease. SARS-CoV-2 itself may predispose to cardiac decompensation; the incidence of heart failure has been recorded as between 23 – 33% in severely- critically ill hospitalized patients [8, 9]. It is therefore important to monitor closely for heart failure, which could be exacerbated by the presence of HCQ. Secondly, there has been some suggestion of prophylactic use of HCQ against SARS-CoV-19 infection; if this translates into clinical practice, then there will have to be robust processes for assessing cardiovascular risk in HCQ recipients.

This case highlights one of the lesser recognized side effects of HCQ, and the potential for severe cardiac dysfunction. As this drug continues to garner interest as a potential weapon in the battle against SARS-CoV-19, it is important to recognize the potential for cardiac decompensation in patients who are already at increased risk of myocardial dysfunction.

Funding

No funding was received for this article

Acknowledgements

We acknowledge the contribution from Dr Andrew Elkington in providing the cardiac MRI scans of this patient.

Learning Points

  1. Hydroxychloroquine can cause severe ventricular systolic impairment, which may resolve on withdrawal of the agent
  2. Patients hospitalized with SARS-CoV-2 are more likely to have pre-existing cardiovascular conditions, and have also been shown to be at increased risk of cardiac decompensation
  3. Clinicians must be aware of the risks to cardiac function when using hydroxychloroquine in the treatment of patients with SARS-CoV-2.

First Author biography

Dr Lindsey Tilling (BSc, MRCP, PhD) is a consultant cardiologist at the Royal Berkshire hospital, and is the lead for heart failure. She has a specialist interest in all aspects of heart function, cardiomyopathy, and device therapy.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad